title: Advanced age in horses affects divisional history of T cells and inflammatory cytokine production.
abstract: A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-inflammatory cytokines both in vitro and in vivo. While lymphocytes from old horses exhibit decreased proliferation, this is not the result of increased apoptosis. Instead, a larger percentage of the T cells remain in the parent generation and produce significant amounts of IFNgamma. Likewise, old horses have increased frequency of CD8-IFNgamma+ T cells and TNFalpha producing cells. We also show that old horses have elevated levels of IL-1beta, IL-15, IL-18 and TNFalpha gene expression in peripheral blood and significant levels of TNFalpha protein in serum, all characteristics of inflamm-aging.
authors.affiliation: Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099, United States.
authors.forename: A A
authors.initials: AA
authors.lastname: Adams
authors.forename: C C
authors.initials: CC
authors.lastname: Breathnach
authors.forename: M P
authors.initials: MP
authors.lastname: Katepalli
authors.forename: K
authors.initials: K
authors.lastname: Kohler
authors.forename: D W
authors.initials: DW
authors.lastname: Horohov
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006736:Horses; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D008934:Mitogens / Q000494:pharmacology; D023421:Models, Animal; D012333:RNA, Messenger / Q000097:blood; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D008934:Mitogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma